EzCatDB: D00232
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DB codeD00232
RLCP classification1.13.10900.462 : Hydrolysis
CATH domainDomain 13.40.390.10 : Collagenase (Catalytic Domain)Catalytic domain
Domain 22.110.10.10 : Hemopexin
E.C.3.4.24.7

CATH domainRelated DB codes (homologues)
2.110.10.10 : HemopexinM00101
3.40.390.10 : Collagenase (Catalytic Domain)S00394,S00395,S00397,S00398,S00399,D00236,M00101

Enzyme Name
UniProtKBKEGG

P21692P03956
Protein nameInterstitial collagenaseInterstitial collagenaseinterstitial collagenase
vertebrate collagenase
matrix metalloproteinase 1
SynonymsEC 3.4.24.7
Matrix metalloproteinase-1
MMP-1
EC 3.4.24.7
Matrix metalloproteinase-1
MMP-1
Fibroblast collagenase
Contains18 kDa interstitial collagenase
22 kDa interstitial collagenase
27 kDa interstitial collagenase
RefSeqNP_001159701.1 (Protein)
NM_001166229.1 (DNA/RNA sequence)
NP_002412.1 (Protein)
NM_002421.3 (DNA/RNA sequence)
MEROPSM10.001 (Metallo)
M10.001 (Metallo)
PfamPF00045 (Hemopexin)
PF00413 (Peptidase_M10)
PF01471 (PG_binding_1)
[Graphical view]
PF00045 (Hemopexin)
PF00413 (Peptidase_M10)
PF01471 (PG_binding_1)
[Graphical view]


UniProtKB:Accession NumberP21692P03956
Entry nameMMP1_PIGMMP1_HUMAN
ActivityCleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N- terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1'' is a hydrophobic residue.Cleavage of the triple helix of collagen at about three-quarters of the length of the molecule from the N- terminus, at 775-Gly-|-Ile-776 in the alpha-1(I) chain. Cleaves synthetic substrates and alpha-macroglobulins at bonds where P1'' is a hydrophobic residue.
Subunit
Interacts with HIV-1 Tat.
Subcellular locationSecreted, extracellular space, extracellular matrix (By similarity).Secreted, extracellular space, extracellular matrix (Probable).
CofactorBinds 4 calcium ions per subunit.,Binds 2 zinc ions per subunit.Binds 4 calcium ions per subunit.,Binds 2 zinc ions per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00038C00076C00211C00001C02898C00017C00012
CompoundZincCalciumCollagenH2Oalpha-MacroglobulinProteinPeptide
Typeheavy metaldivalent metal (Ca2+, Mg2+)amine group,carboxyl group,peptide/proteinH2Opeptide/proteinpeptide/proteinpeptide/protein
ChEBI29105
29108

15377




PubChem32051
271

962
22247451




                
1fblA01Bound:2x_ZNBound:3x_CAUnbound UnboundUnboundUnboundIntermediate-analogue:HTA
1aykABound:2x_ZNBound:_CAUnbound UnboundUnboundUnboundUnbound
1cgeABound:2x_ZNBound:3x_CAUnbound UnboundUnboundUnboundUnbound
1cgfABound:2x_ZNBound:3x_CAUnbound UnboundUnboundUnboundUnbound
1cgfBBound:2x_ZNBound:3x_CAUnbound UnboundUnboundUnboundUnbound
1cglABound:2x_ZNBound:_CAUnbound UnboundUnboundUnboundIntermediate-analogue:PHQ-ABU-LEU-PHE-EMR(chain C)
1cglBBound:2x_ZNBound:_CAUnbound UnboundUnboundUnboundIntermediate-analogue:PHQ-ABU-LEU-PHE-EMR(chain D)
1hfcABound:2x_ZNBound:_CAUnbound UnboundUnboundUnboundIntermediate-analogue:PLH
1su3A01Bound:2x_ZNBound:3x_CAUnbound UnboundUnboundUnboundUnbound
1su3B01Bound:2x_ZNBound:3x_CAUnbound UnboundUnboundUnboundUnbound
2aykABound:2x_ZNBound:_CAUnbound UnboundUnboundUnboundUnbound
2tclABound:2x_ZNBound:2x_CAUnbound UnboundUnboundUnboundIntermediate-analogue:RO4
3aykABound:2x_ZNBound:_CAUnbound UnboundUnboundUnboundIntermediate-analogue:CGS
4aykABound:2x_ZNBound:_CAUnbound UnboundUnboundUnboundIntermediate-analogue:CGS
966cABound:2x_ZNBound:3x_CAUnbound UnboundUnboundUnboundIntermediate-analogue:RS2
1fblA02UnboundBound:_CAUnbound UnboundUnboundUnboundUnbound
1su3A02UnboundBound:_CAUnbound UnboundUnboundUnboundUnbound
1su3B02UnboundBound:_CAUnbound UnboundUnboundUnboundUnbound

Active-site residues
resource
Swiss-prot;P21692, P03956
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysis
           
1fblA01ASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1aykAASN  80;GLU 119
HIS  68;ASP  70;HIS  83;HIS  96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc)
ALA  82
1cgeAASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1cgfAASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1cgfBASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1cglAASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1cglBASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1hfcAASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1su3A01ASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1su3B01ASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
2aykAASN  80;GLU 119
HIS  68;ASP  70;HIS  83;HIS  96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc)
ALA  82
2tclAASN  80;GLU 119
HIS  68;ASP  70;HIS  83;HIS  96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc)
ALA  82
3aykAASN  80;GLU 119
HIS  68;ASP  70;HIS  83;HIS  96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc)
ALA  82
4aykAASN  80;GLU 119
HIS  68;ASP  70;HIS  83;HIS  96(Non-catalytic zinc);HIS 118;HIS 122;HIS 128(Catalytic zinc)
ALA  82
966cAASN 180;GLU 219
HIS 168;ASP 170;HIS 183;HIS 196(Non-catalytic zinc);HIS 218;HIS 222;HIS 228(Catalytic zinc)
ALA 182
1fblA02 
 
 
1su3A02 
 
 
1su3B02 
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[6]Fig.5, p.8213-8214
[8]Fig.11, p.107-108
[9]p.376

references
[1]
PubMed ID2153297
JournalProc Natl Acad Sci U S A
Year1990
Volume87
Pages364-8
AuthorsSpringman EB, Angleton EL, Birkedal-Hansen H, Van Wart HE
TitleMultiple modes of activation of latent human fibroblast collagenase: evidence for the role of a Cys73 active-site zinc complex in latency and a "cysteine switch" mechanism for activation.
[2]
PubMed ID1480035
JournalMatrix Suppl
Year1992
Volume1
Pages259-62
AuthorsGalardy RE, Grobelny D, Kortylewicz ZP, Poncz L
TitleInhibition of human skin fibroblast collagenase by phosphorus-containing peptides.
[3]
PubMed ID1313176
JournalProteins
Year1992
Volume12
Pages42-8
AuthorsLowry CL, McGeehan G, LeVine H 3rd
TitleMetal ion stabilization of the conformation of a recombinant 19-kDa catalytic fragment of human fibroblast collagenase.
[4]
PubMed ID7978813
JournalAnn N Y Acad Sci
Year1994
Volume732
Pages375-8
AuthorsLovejoy B, Cleasby A, Hassell AM, Luther MA, Weigl D, McGeehan G, Lambert MH, Jordan SR
TitleStructural analysis of the catalytic domain of human fibroblast collagenase.
[5]
PubMed ID7944383
JournalArch Biochem Biophys
Year1994
Volume314
Pages120-5
AuthorsBrownell J, Earley W, Kunec E, Morgan BA, Olyslager B, Wahl RC, Houck DR
TitleComparison of native matrix metalloproteinases and their recombinant catalytic domains using a novel radiometric assay.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 102-269.
PubMed ID8031754
JournalBiochemistry
Year1994
Volume33
Pages8207-17
AuthorsLovejoy B, Hassell AM, Luther MA, Weigl D, Jordan SR
TitleCrystal structures of recombinant 19-kDa human fibroblast collagenase complexed to itself.
Related PDB1cge,1cgf
Related UniProtKBP03956
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 100-269.
Medline ID95384760
PubMed ID7656013
JournalNat Struct Biol
Year1994
Volume1
Pages106-10
AuthorsBorkakoti N, Winkler FK, Williams DH, D'Arcy A, Broadhurst MJ, Brown PA, Johnson WH, Murray EJ
TitleStructure of the catalytic domain of human fibroblast collagenase complexed with an inhibitor.
Related PDB2tcl
Related UniProtKBP03956
[8]
CommentsX-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 101-269.
PubMed ID8090713
JournalProteins
Year1994
Volume19
Pages98-109
AuthorsSpurlino JC, Smallwood AM, Carlton DD, Banks TM, Vavra KJ, Johnson JS, Cook ER, Falvo J, Wahl RC, Pulvino TA, et al
Title1.56 A structure of mature truncated human fibroblast collagenase.
Related PDB1hfc
Related UniProtKBP03956
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 102-269.
Medline ID94105765
PubMed ID8278810
JournalScience
Year1994
Volume263
Pages375-7
AuthorsLovejoy B, Cleasby A, Hassell AM, Longley K, Luther MA, Weigl D, McGeehan G, McElroy AB, Drewry D, Lambert MH, et al
TitleStructure of the catalytic domain of fibroblast collagenase complexed with an inhibitor.
Related PDB1cgl
Related UniProtKBP03956
[10]
CommentsX-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 100-469
Medline ID96173003
PubMed ID8590015
JournalStructure
Year1995
Volume3
Pages541-9
AuthorsLi J, Brick P, O'Hare MC, Skarzynski T, Lloyd LF, Curry VA, Clark IM, Bigg HF, Hazleman BL, Cawston TE, et al
TitleStructure of full-length porcine synovial collagenase reveals a C-terminal domain containing a calcium-linked, four-bladed beta-propeller.
Related PDB1fbl
Related UniProtKBP21692
[11]
PubMed ID9063449
JournalEur J Biochem
Year1997
Volume244
Pages81-8
AuthorsVallon R, Muller R, Moosmayer D, Gerlach E, Angel P
TitleThe catalytic domain of activated collagenase I (MMP-1) is absolutely required for interaction with its specific inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1).
[12]
PubMed ID9335112
JournalJ Biomol NMR
Year1997
Volume10
Pages9-19
AuthorsMoy FJ, Pisano MR, Chanda PK, Urbano C, Killar LM, Sung ML, Powers R
TitleAssignments, secondary structure and dynamics of the inhibitor-free catalytic fragment of human fibroblast collagenase.
[13]
CommentsSTRUCTURE BY NMR OF 101-269.
Medline ID98145213
PubMed ID9484219
JournalBiochemistry
Year1998
Volume37
Pages1495-504
AuthorsMoy FJ, Chanda PK, Cosmi S, Pisano MR, Urbano C, Wilhelm J, Powers R
TitleHigh-resolution solution structure of the inhibitor-free catalytic fragment of human fibroblast collagenase determined by multidimensional NMR.
Related PDB1ayk
Related UniProtKBP03956
[14]
PubMed ID9844107
JournalJ Bone Miner Res
Year1998
Volume13
Pages1890-902
AuthorsKremer EA, Chen Y, Suzuki K, Nagase H, Gorski JP
TitleHydroxyapatite induces autolytic degradation and inactivation of matrix metalloproteinase-1 and -3.
[15]
PubMed ID10548534
JournalBiochem J
Year1999
Volume344 Pt 1
Pages61-8
AuthorsLittle CB, Flannery CR, Hughes CE, Mort JS, Roughley PJ, Dent C, Caterson B
TitleAggrecanase versus matrix metalloproteinases in the catabolism of the interglobular domain of aggrecan in vitro.
[16]
CommentsNMR Structure
PubMed ID10353819
JournalBiochemistry
Year1999
Volume38
Pages7085-96
AuthorsMoy FJ, Chanda PK, Chen JM, Cosmi S, Edris W, Skotnicki JS, Wilhelm J, Powers R
TitleNMR solution structure of the catalytic fragment of human fibroblast collagenase complexed with a sulfonamide derivative of a hydroxamic acid compound.
Related PDB3ayk,4ayk
[17]
PubMed ID10074939
JournalNat Struct Biol
Year1999
Volume6
Pages217-21
AuthorsLovejoy B, Welch AR, Carr S, Luong C, Broka C, Hendricks RT, Campbell JA, Walker KA, Martin R, Van Wart H, Browner MF
TitleCrystal structures of MMP-1 and -13 reveal the structural basis for selectivity of collagenase inhibitors.
Related PDB966c
[18]
PubMed ID11082208
JournalEur J Biochem
Year2000
Volume267
Pages6943-50
AuthorsSaito M, Sato K, Kunisaki N, Kimura S
TitleCharacterization of a rainbow trout matrix metalloproteinase capable of degrading type I collagen.
[19]
PubMed ID10871619
JournalJ Biol Chem
Year2000
Volume275
Pages29610-7
AuthorsChung L, Shimokawa K, Dinakarpandian D, Grams F, Fields GB, Nagase H
TitleIdentification of the (183)RWTNNFREY(191) region as a critical segment of matrix metalloproteinase 1 for the expression of collagenolytic activity.
[20]
PubMed ID10926524
JournalJ Mol Biol
Year2000
Volume301
Pages513-24
AuthorsZhang X, Gonnella NC, Koehn J, Pathak N, Ganu V, Melton R, Parker D, Hu SI, Nam KY
TitleSolution structure of the catalytic domain of human collagenase-3 (MMP-13) complexed to a potent non-peptidic sulfonamide inhibitor: binding comparison with stromelysin-1 and collagenase-1.
[21]
PubMed ID11677139
JournalBioorg Med Chem Lett
Year2001
Volume11
Pages2975-8
AuthorsLevin JI, Chen JM, Du MT, Nelson FC, Wehr T, DiJoseph JF, Killar LM, Skala S, Sung A, Sharr MA, Roth CE, Jin G, Cowling R, Di L, Sherman M, Xu ZB, March CJ, Mohler KM, Black RA, Skotnicki JS
TitleThe discovery of anthranilic acid-based MMP inhibitors. Part 3: incorporation of basic amines.
[22]
PubMed ID11113146
JournalJ Biol Chem
Year2001
Volume276
Pages10253-62
AuthorsBalbin M, Fueyo A, Knauper V, Lopez JM, Alvarez J, Sanchez LM, Quesada V, Bordallo J, Murphy G, Lopez-Otin C
TitleIdentification and enzymatic characterization of two diverging murine counterparts of human interstitial collagenase (MMP-1) expressed at sites of embryo implantation.
[23]
PubMed ID11593430
JournalOncogene
Year2001
Volume20
Pages6215-24
AuthorsBosc DG, Goueli BS, Janknecht R
TitleHER2/Neu-mediated activation of the ETS transcription factor ER81 and its target gene MMP-1.
[24]
PubMed ID12595271
JournalJ Mol Biol
Year2003
Volume326
Pages1651-65
AuthorsKallblad P, Dean PM
TitleEfficient conformational sampling of local side-chain flexibility.
[25]
PubMed ID15611040
JournalJ Biol Chem
Year2005
Volume280
Pages9578-85
AuthorsJozic D, Bourenkov G, Lim NH, Visse R, Nagase H, Bode W, Maskos K
TitleX-ray structure of human proMMP-1: new insights into procollagenase activation and collagen binding.
Related PDB1su3

comments
Although this enzyme binds four calcium ions and two zinc ions, all the calcium ions and one of the zinc ions are not involved in catalysis.
According to the literature [6], [8] & [9], this enzyme is partially and distantly homologous to thermolysin (D00234 in EzCatDB; CATH 3.10.170.10), although it is differently classified in the CATH database.
According to the literature [6] & [9] suggested that the catalytic zinc ion of this enzyme, which is bound to three histidine residues, might have a higher net positive charge and a greater ability to stabilize the negative charge in the transition-state than the counterpart zinc, bound to two histidine residues and an acidic residue, in thermolysin (D00234 in EzCatDB).
According to the literature [6], [8] & [9], the catalytic reaction proceeds as follows:
(1) Carbonyl oxygen of target bond and hydrolytic water molecule are bound to zinc ion, which facilitates the catalysis. Glu219 (of 1fbl) acts as a general base to deprotonate and activate the water molecule.
(2) The water molecule makes a nucleophilic attack on the carbonyl carbon to form a tetrahedral intermediate.
(3) The intermediate is stabilized by Asn180 and mainchain carbonyl of Ala113, together with the zinc ion. Here, Asn112 and mainchain carbonyl group of Ala113 stabilize the leaving amine group. The zinc ion stabilizes the negative charge on the hydroxyl anion and the new hydroxyl group (originally water).
(4) Glu219 acts as a genral acid to protonate the leaving amine group. (Glu143 may also shuttle the remaining proton from the hydroxyl group to the amine to complete the bond cleavage.)

createdupdated
2005-02-162009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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